• Glibenclamide;
  • levcromakalim;
  • potassium channels;
  • iberiotoxin;
  • cyanide;
  • potassium channel opener;
  • resting membrane potential;
  • urethra;
  • urethral resting tone
  • 1
    The effects of levcromakalim (BRL 38227) on ionic currents recorded from pig proximal urethra were investigated by use of tension measurement and patch clamp techniques (conventional whole-cell configuration, nystatin perforated patch, and cell-attached configuration).
  • 2
    Levcromakalim (1 μm) caused a relaxation in the resting tone. This levcromakalim-induced relaxation was inhibited by the pretreatment with 1 μm glibenclamide.
  • 3
    The resting membrane potential recorded from single cells in current-clamp mode was −36.1 ± 4.4 mV (n = 5).
  • 4
    Levcromakalim induced a concentration-dependent hyperpolarization with a maximum (at ≥ 10 μm) close to the theoretical equilibrium potential of potassium (EK). The membrane hyperpolarization caused by 1 μm levcromakalim (24.7 ± 5.8 mV, n = 4) was abolished by 1 μm glibenclamide.
  • 5
    Levcromakalim (100 μm) caused an outward K current in whole-cell recordings which was unaffected by iberiotoxin (300 nM) but abolished by glibenclamide (10 μm).
  • 6
    In cell-attached patches, levcromakalim activated a 43 pS K channel which was inhibited by the application of glibenclamide.
  • 7
    The metabolic poison, cyanide (CN), also activated a 43 pS K channel which was suppressed by the application of 10 μm glibenclamide.
  • 8
    These results indicate that levcromakalim and metabolic inhibition activate the same 43 pS K channel in pig proximal urethra. The resultant urethral hyperpolarization might reduce the usefulness of K channel openers in the treatment of detrusor instability, but be of value in treating outflow obstruction.